Linzhao Cheng

CHENG: I did my Ph.D. at Johns Hopkins in the Department of Molecular Biology and Genetics on DNA replication. Basically, I was studying how the cell copies the DNA and then passes it from one generation to another. Then I became interested in how whole cells were able to copy themselves. Gradually I became fascinated by stem cells because these cells can duplicate themselves forever. One step at a time, I moved onto the stem cell field of today.

So you didn’t move into stem cell research because it was the next big thing?

CHENG: Normally, I don’t want to jump in on what everyone else is doing. I started working on stem cells in the early 1990’s when they weren’t nearly as popular as they are today.

Back then if someone sitting next to me on an airplane asked me what I did, I would tell them that I am a scientist and I study stem cells. Typically that was met with silence because no one knew what I was talking about. On many occasions, I had to label myself as a developmental biologist. About 10 years ago, the field began to change tremendously. Now when I say I work on stem cells, people everywhere want to talk about the promise and ethical issues in casual conversation.

I hear you used to work in industry. Why did you move back to academics?

CHENG: I wanted to do innovative research with the freedom that you get at an academic institution. And at the time, while I felt the stem cell technology wasn’t ready to move to clinical trials, the company pushed for such trials under investor pressure. I reached the conclusion that either this company isn’t good for me or I’m not good for the company. So I came to Hopkins as a faculty member in 1999, but still continued working on human stem cells.

Do you think that starting your career in industry affects how you run your lab today?

CHENG: My industry job had a tremendous influence on not only what I’m doing, but the style in which I’m doing the science. It helps me to be more focused and efficient.

To me medicine is a form of engineering. I’m always trying to do something to help the patient. Science should not only be beautiful, but useful as well.

I have always worked with human stem cells so I didn’t see any point in switching to animal models like many other people. Sure, human stem cells are difficult to work with and experiments can take longer to do than using animal models. Fortunately it’s paying off and we’re making progress. Recent research on human stem cells has changed human biology. Because of the newest stem cell technology, we have sources of cells from people with specific genetic diseases that we can now use to develop new treatments.

So what kind of stem cell research do you do?

CHENG: We are most interested in the stem cells that make blood. We would like to find a better way to generate blood cells for research and for transplantation without continually having to always ask for blood donations. Hopefully in the future we will be able to make an unlimited supply of blood from induced pluripotent stem (iPS) cells —stem cells made from adult cells in the body—either from the patients themselves who need transfusions or from universal donors.

In the U.S., donor blood shortages occur immediately after the summer and during disasters. Occasionally, contamination issues deplete the blood supply. If we can develop the technology to make an unlimited, clean supply of blood, then we wouldn’t have so many setbacks when crises like these occur.

How close are you toward this goal?

CHENG: We are making progress but we first have to overcome some technical hurdles. First of all, we have to generate a sufficient supply of iPS cells and then we have to turn them into blood cells.

We have developed a less invasive and quicker way to make iPS cells from patient’s blood samples. The current way of getting iPS cells is to take a skin biopsy and then grow these skin cells in the lab for four to six weeks. But, we have developed a way to use a single, small blood draw, typical of any doctor’s office blood draw, grow those cells in the lab for about 10 days and then generate iPS cells. It’s much faster and more efficient.

So we have one hurdle down and another to go. Now, I hope that I can take advantage of my colleagues’ expertise and develop a new method to efficiently generate blood cells from iPS cells in the laboratory.

--Interviewed by Vanessa McMains

Linzhao Cheng on making stem cells from a patient's blood sample:

Video transcription: "The recent advance of this field is very exciting or even we can say evolutionary. And that is the technology called iPS cells—or the induced pluripotent stem cells. Basically it’s the evolutionary technique, where we can convert the adult cells -- such as skin, such as other cell types -- to the very early primitive stage, the state that would be very similar to the cells isolated or derived from the early embryo, such as embryonic stem cells. They can proliferate, they can be expanded in the laboratory forever, but they can also generate one of the 220 different cell types.

"One contribution that we made to the field is that we can generate iPS cells safer and and cleaner iPS cells from the periphery blood, just from a blood draw, so that we don’t have to use the skin biopsy. Not only does it take shorter time, for example, from 10 days versus four to six weeks, but also we found out that it’s more efficient after we overcome some of the technical hurdles. Since we can derive iPS cells from the patient with a particular type of the disease with a particular type of the mutation, so it’s probably the first time that we can link the human genetics to the human cell biology or biochemistry."